The Production of a Rat Model That Inhibits Phosphoenolpyruvate Carboxykinase (PEPCK), a Rate-Limiting Enzyme of Hepatic Gluconeogenesis

We previously showed that taurine administration contributed to the extension of time to exhaustion through exercise-induced hypoglycemia restraint, and we suggested that the activation of hepatic gluconeogenesis was initiated before the exercise with the taurine administration. We hypothesize that the extension effect of exercise duration with the taurine administration is restrained in the rats which inhibited hepatic gluconeogenesis. In this study, we aimed to produce a rat model that inhibited hepatic gluconeogenesis as a first step in testing our hypothesis.F344 male rats of 8 weeks after birth were purchased. The blood samples were collected via jugular vein catheter to perform the pyruvate tolerance test (PTT) with the intraperitoneal administration, and to determine the optimal time point of blood glucose measurement. 3-mercaptopicolinic acids (3MPA) was used as an inhibitor of PEPCK. The rats were divided into three groups, Non-dosage control (CON) group, 30 mg/kg・BW 3MPA (3MPA 30) group, and 300 mg/kg・BW 3MPA (3MPA 300) group.The blood glucose level showed a significant peak 15 min after pyruvate administration. The change of the blood glucose level after the PTT in 3MPA 300 group was significantly smaller than that of the CON group at this time point. These results show we could prepare the rat model that inhibited hepatic gluconeogenesis.

Hepatic glucose production; Prolonged exercise; Running performance.